PROJECT SUMMARY: Research Project 3 We propose Research Project 3 (RP3) in the context of a P50 Research Center of Excellence: The Center for Translational and Prevention Science (CTAPS). CTAPS has been funded continuously since 2003 (P20MH068666; P30DA027827) to advance next-generation basic and preventive investigations of risk, resilience, and drug use among African American young people living in resource-poor communities in the southeastern US. Informed by advances that NIDA neuroscientists have made, we recently expanded our program to consider the influence of social adversity on the consumption of high fat/high sugar foods, which also can be considered an addictive behavior, co-opting many of the same neural circuitries as does drug abuse. Understanding the development and prevention of addictive behavior vulnerabilities has significant implications for preventing both drug abuse and cardiometabolic disease. The proposed P50 is designed to transform scientific understanding regarding the etiology and prevention of addictive behavior by testing hypotheses suggested by a neuroimmune network (NIN) model that, in concert with familial and contextual factors, contributes to the development of drug use, unhealthy eating habits, and cardiometabolic health problems. In RP3, we focus on rural African American families in Georgia in which poverty and unemployment rates are among the highest in the nation. The parents in these families have grown up taking part in the Strong African American Families Healthy Adolescent/Adult Project (SHAPE; R01HD030588). In RP3, we propose to leverage the SHAPE sample to test hypotheses regarding how addictive behavior vulnerabilities are transmitted across generations. We propose to investigate multigenerational risk and resilience pathways linking chronic SES- and race-related stress, parenting behavior, and risk factors suggested by the NIN model to preadolescent children?s addictive behavior vulnerability and cardiometabolic risk. We will combine extant data on grandparents and parents, data currently being collected from parents that R01HD030588 is funding, and collection of new data from parents and children that this proposal will support. Our first aim is to investigate the risk pathways through which SES- and race-related stress exposure across generations affects children?s addictive behavior vulnerabilities and cardiometabolic health. Our primary endpoints are children?s (~age 11) addictive behavior vulnerabilities and cardiometabolic health. We hypothesize that exposure to SES- and race-related stressors promotes a chain of processes generations that affects children?s vulnerabilities to addictive behavior and their cardiometabolic health. The mechanisms through which SES- and race-related stress promote children?s addictive behavior vulnerability and cardiometabolic risk include (a) use of harsh, unsupportive parenting practices and, (b) NIN risk factors (inflammation and behavior- and emotion-regulation difficulties suggested by the NIN model), and (c) addictive behavior (parents? use of alcohol, nicotine, and other drugs, as well as their unhealthy eating.